The research proposed has three overall objectives: To develop general syntheses of cyclobutene analogs of benzodiazepines; To preliminarily screen a variety of these compounds, in animal test systems, for benzodiazepine activity; and Based on the preliminary results, to test in detail the effects of structure (stereo-chemistry and acid-base characteristics) on the activities of benzodiazepine precursors so as to fine tune the products toward greater clinical specificity. The goal was to systematically synthesize and test novel benzodiazepines in order to seek new compounds with some degree of specificity for one of the useful actions of one of these drugs. Benzodiazepines are useful because of the antianxiety, anticonvulsant, muscle relaxant, sedative and hypnotic properties. A compound's usefulness is maximized if it can be made highly selective. For example, an anticonvulsant with no other benzodiazepine actions would be extremely desirable. Likewise, a centrally acting muscle relaxant devoid of sedative properties would be a major advance in treating a wide variety of medical and surgical patients. Testing novel benzodiazepine-like compounds, such as the sulfur analogs, may yield new drugs with a greater degree of selectivity. During the current year synthetic routes to specific benzodiazepine analogs have been developed and practical syntheses completed. Some of these synthetic products are now being tested.